Nimodipine Calcium-channel blockers

Calcium channel blockers Nicardapine (i) Nimodipine (i) Nitrendipine (i)... 

Calcium Channel Blockers. The calcium channel blockers work by blocking the influx of calcium, an excitatory ion, into the cell. The first calcium channel blocker, verapamil (Calan), was introduced in the 1960s. Others, including diltiazem, nifedipine, and nimodipine, are now available. The calcium channel blockers have been used to treat a variety of medical conditions including high blood pressure, cardiac pain (angina) and arrhythmias, migraines, seizure disorders, and premature labor. 

Other options - ECT possibly calcium channel blockers such as verapamil or nimodipine. 

Alternate treatments. Mood-stabilization and control of manic or hy-pomanic episodes in some subtypes of bipolar illness may also be achieved with the anticonvulsants valproate and carbamazepine, as well as with calcium channel blockers (e.g., verapamil, nifedipine, nimodipine). Effects are delayed and apparently unrelated to the mechanisms responsible for anticonvulsant and cardiovascular actions, respectively. 

The effects of the prototypical calcium channel blockers are seen most prominently in the cardiovascular system (Table 19.1), although calcium channels are widely distributed among excitable cells. The following calcium channel-blocking drugs are clinically the most widely used compounds in this very extensive class of pharmacological agents amlodipine, diltiazem, isradipine, nifedipine, nicardipine, nimodipine, and verapamil. 

Oarbamazepine is increasingly recognized as an effective treatment for bipolar affective illness, whereas the data on nimodipine and related calcium channel blockers [CCBs] are much more preliminary. In this chapter, we review data on the efficacy and putative mechanisms of action of carbamazepine and nimodipine in the recurrent affective disorders. 

FKiURE 6 5C. Efficacy of dihydropyridine L-type calcium channel blockers. Mean deviation from euthymia ratings (number of days in parentheses) in a patient with bipolar 11 disorder with ultra-ultrarapid cycling showing the following efficacy of nimodipine monotherapy efficacy of nimodipine-carbamazepine combination therapy unsuccessful transition from nimodipine to verapamil successful reinstitution of nimodipine-carbamazepine combination therapy and, finally, successful transition to isradipine-carbamazepine combination therapy. P <. 05 "nimodipine slowly tapered to zero. 

Jarvik LF Calcium channel blocker nimodipine for primary degenerative dementia. Biol Psychiatry 30 1171-1172, 1991... 

Calcium channel blockers with vasodilator effects, such as nifedipine, nicardipine, and nimodipine, will potentiate the effect of vasodilator effects of, e.g. halothane or isoflurane, potentiating any hypotension. This is especially obvious in hypertensive patients and when combined with similarly acting agents, such as sodium nitroprusside or nitroglycerin. Similarly, they also enhance the tendency of volatile anaesthetics to reduce hypoxic pulmonary vasoconstriction, which might exacerbate ventilation/perfusion mismatching during anaesthesia. 

Important differences in vascular selectivity exist among the calcium channel blockers. In general, the dihydropyridines have a greater ratio of vascular smooth muscle effects relative to cardiac effects than do diltiazem and verapamil. Furthermore, the dihydropyridines may differ in their potency in different vascular beds. For example, nimodipine is claimed to be particularly selective for cerebral blood vessels. Splice variants in the structure of the cq channel subunit appear to account for these differences. 

Nimodipine, a member of the dihydropyridine group of calcium channel blockers, has a high affinity for cerebral blood vessels and appears to reduce morbidity after a subarachnoid hemorrhage. Nimodipine was approved for use in patients who have had a hemorrhagic stroke, but it has recently been withdrawn. Nicardipine has similar effects and is used by intravenous and intracerebral arterial infusion to prevent cerebral vasospasm associated with stroke. Verapamil as well, despite its lack of vasoselectivity, is used by the intra-arterial route in stroke. Some evidence suggests that calcium channel blockers may also reduce cerebral damage after thromboembolic stroke. 

Calcium channel blockers, such as verapamil (Calan , Covera , Isoptin , Verelan), diltiazem (Cardizem , Dilacor , Tiazac ), and nimodipine (Nimotop ), inhibit the flow of calcium ions into the cells that line blood vessel walls. This changes the way the blood vessels surrounding the brain dilate and constrict and provides relief from migraines. 

In the derivatives bearing a stereogenic center at C-4, such as nicardipine, nimodipine, nitrendipine (42), felodipine (43), isradipine (44) and niguldip-ine (45), both stereoisomers differ markedly in their potencies as calcium channel blockers but they are about equally effective as MDR reversal mod-ulatores [80,81]. This has led to use of the R isomers as MDR modulators, as in the case of dexniguldipine (45). 

It has been suggested that calcium channel blockers can be used to treat cocaine dependence, and some studies have shown reductions in cocaine-induced subjective and cardiovascular responses with nifedipine and diltiazem. The cardiovascular and subjective responses to cocaine have been evaluated in a double-blind, placebo-controlled, crossover study in five subjects pretreated with two dosage of nimodipine (393). Nimodipine 60 mg attenuated the rise in systolic, but not diastolic, blood pressure after cocaine. In three subjects nimodipine 90 mg produced greater attenuation than 60 mg. The subjective effects of cocaine were not altered by either dose of nimodipine. 

CALCIUM CHANNEL BLOCKERS SSRIs Reports oft serum levels of nimodipine and episodes of adverse effects of nifedipine and verapamil (oedema, flushing and i BP) attributed to t levels when co-administered with fluoxetine Fluoxetine inhibits CYP3A4-mediated metabolism of calcium channel blockers. It also inhibits intestinal P-gp, which may t the bioavailability of verapamil Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider reducing the dose of calcium channel blocker or using an alternative antidepressant... 

CALCIUM CHANNEL BLOCKERS BARBITURATES L plasma concentrations of felodipine, nifedipine, nimodipine, nisoldipine and verapamil with phenobarbital Phenobarbital induces CYP3A4, which metabolizes calcium channel blockers. It also induces intestinal P-gp, which may 1 the bioavailability of verapamil Monitor PR and BP closely watch for Tbp... 

CALCIUM CHANNEL BLOCKERS CARBAMAZEPINE 1. Diltiazem and verapamil T plasma concentrations of carbamazepine (cases of toxicity) 2.1 plasma concentrations of felodipine, nifedipine and possibly nimodipine and nisoldipine 1. Diltiazem and verapamil inhibit CYP3A4-mediated metabolism of carbamazepine. They also inhibit intestinal P-gp, which may t the bioavailability of carbamazepine 2. Carbamazepine, in turn, induces CYP3A4, which metabolizes calcium channel blockers 1. Monitor carbamazepine levels when initiating calcium channel blockers, particularly diltiazem and verapamil 2. Monitor PR and BP closely watch for T BP when starting carbamazepine in patients already on calcium channel blockers... 

CALCIUM CHANNEL BLOCKERS SODIUM VALPROATE Nimodipine levels may be t by valproate Uncertain at present Monitor BP at least weekly until stable. Warn patients to report symptoms of hypotension (light-headedness, dizziness on standing, etc.)... 

CALCIUM CHANNEL BLOCKERS GRAPEFRUIT JUICE t bioavailability of felodipine and nisoldipine (with reports of adverse effects), and t bioavailability of isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine and verapamil (without reported adverse clinical effects) Postulated that flavonoids in grapefruit juice (and possibly Seville oranges and limes) inhibit intestinal (but not hepatic) CYP3A4. They also inhibit intestinal P-gp, which may t the bioavailability of verapamil Avoid concurrent use of felodipine and nisoldipine and grapefruit juice... 

CALCIUM CHANNEL BLOCKERS NON-DEPOLARIZING t effect of non-depolarising muscle relaxants with parenteral calcium channel blockers the effect is less certain with oral therapy. In two cohort studies, vecuronium requirements were halved in patients on diltiazem. Nimodipine does not seem to share this interaction Uncertain postulated that ACh release at the synapse is calcium dependent 1 calcium concentrations at the nerve ending may 1 ACh release, which in turn prolongs the nerve blockade Monitor nerve blockade carefully in patients on calcium channel blockers, particularly near to the end of surgery, when muscle relaxation may be prolonged and difficult to reverse... 

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